Hepatocarcinoma is roughly divided into a primary hepatocarcinoma developed in the liver and a metastatic hepatocarcinoma. Ninety percent of the primary hepatocarcinoma is said to be hepatocellular carcinoma.
Hepatocellular carcinoma patients often have hepatitis C virus or hepatitis B virus infection as an underlying disease. Acute viral hepatitis is developed into chronic viral hepatitis and further into cirrhosis. Likewise, in most cases, canceration occurs for the first time after a long period of time from the onset of viral hepatitis. In cirrhosis, inflammation and regeneration repeatedly occur, with the result that the number of normal hepatic cells reduces and the liver changes into an organ constituted of fibrous tissue. For example, the number of hepatitis C patients is 3,000,000 in Japan and said to be 10,000,000 or more in China and Africa. Furthermore, in the cases of hepatitis B and C patients, an incidence of cancer from chronic hepatitis, more specifically, an incidence of cancer from mild chronic hepatitis (F1) is 0.8% each year and an incidence of cancer from moderate chronic hepatitis (F2) is 0.9% each year. In contrast, an incidence of cancer from severe chronic hepatitis (F3) becomes 3.5% each year and moreover, the rate of carcinogenesis from cirrhosis (F4) increases up to 7% each year (FIGS. 2, 3). Also, the histology of the hepatic disease changes according to the progression of the state. First, in chronic hepatitis, the function of the liver starts to disappear, and in cirrhosis, a pathological structure appears and fibrosis of the liver advances (FIG. 1).
In cancer therapy, it is important to find cancer in the early stage.
Also in the case of hepatocellular carcinoma, early detection of cancer has a significant effect upon therapy and postoperative prognosis. The 5-year survival rate of partial hepatectomy is 80% in stage-I hepatocarcinoma and only 38% in stage-IV hepatocarcinoma.
As hepatocarcinoma markers, up to present, a-fetoprotein (AFP) and a protein induced by Vitamin K absence or antagonist-II (PIVKA-II) have been known (Patent Literatures 1, 2); however, neither specificity nor sensitivity thereof are sufficient. For this reason, in medical examination presently carried out for early detection of hepatocarcinoma, a hepatocarcinoma marker is used in combination with imaging inspection such as ultrasonographic examination, computed tomography (CT) and nuclear magnetic resonance imaging (MRI).